Autophagy protects against cerebral ischemic reperfusion injury by inhibiting neuroinflammation.

Objective: To examine the effect of autophagy on cerebral damage caused by different models and test the hypothesis that its protection mechanism acts via inhibiting expression of neuroinflammatory mediators.

Methods: Autophagy was induced by rapamycin treatment. Cerebral damage was induced using models of IL-6 treatment, oxygen glucose deprivation/reoxygenation (OGD/R) , and middle cerebral artery occlusion (MCAO) . The effect and mechanism of autophagy was examined and assessed in terms of cell viability, infarction size in brain tissue, neurological score, production of inflammatory mediators IL-1β and IL-6, transcription and protein expression of autophagy markers beclin-1 and LC-3II in different experimental groups.

Results: Autophagy triggered by rapamycin could protect neurons from IL-6-induced injury and astrocytes from OGD/R-induced injury and in rat brain tissue from MCAO . Autophagy significantly increased cell viability, attenuated cerebral infarction and improved neurological scores. It also inhibited production of the IL-1β and IL-6 and elevated the expression of beclin-1 and LC-3II.

Conclusions: Autophagy can inhibit the inflammatory response and reduce cerebral I/R injury. There was a relationship between the extent of protection and (i) the level of the autophagic response, (ii) the stage of the cerebral I/R injury, and (iii) the time of intervention.